Cortical Tension Allocates the First Inner Cells of the Mammalian Embryo

Abstract

Every cell in our body originates from the pluripotent inner mass of the embryo, yet it is unknown how biomechanical forces allocate inner cells in vivo. Here we discover subcellular heterogeneities in tensile forces, generated by actomyosin cortical networks, which drive apical constriction to position the first inner cells of living mouse embryos. Myosin II accumulates specifically around constricting cells, and its disruption dysregulates constriction and cell fate. Laser ablations of actomyosin networks reveal that constricting cells have higher cortical tension, generate tension anisotropies and morphological changes in adjacent regions of neighboring cells, and require their neighbors to coordinate their own changes in shape. Thus, tensile forces determine the first spatial segregation of cells during mammalian development. We propose that, unlike more cohesive tissues, the early embryo dissipates tensile forces required by constricting cells via their neighbors, thereby allowing confined cell repositioning without jeopardizing global architecture.

Lineage specification in the mouse preimplantation embryo

“…More recently, two studies demonstrated that this internalization is mediated by active cellular behaviours (Anani et al, 2014;Samarage et al, 2015). One study focused on inheritance of the apical domain after the 8-cell division and demonstrated that outer apolar cells are actually internalized instead of adopting polarity in intact embryos or in isolated blastomeres (Anani et al, 2014).…”

“…Enrichment of phosphomyosin was observed at the non-contact surface of the outer apolar cells, suggesting that the internalization process is regulated by increased cortical actomyosin contractility. The second study directly observed the internalization process in intact embryos and demonstrated that apical constriction is a driving force of this internalization, although the identity of internalizing cells was not specified (Samarage et al, 2015). Together, these studies suggest that symmetric/asymmetric divisions in this context should be defined by inheritance of the apical domain rather than by division angles, and that apical constriction at the non-contact surface of outer apolar cells initiates apolar cell internalization to establish the outer/inner configuration of polar/apolar cells (Fig.…”

Methods for Spatio-Temporal Analysis of Embryo Cleavage In Vitro

“…Capped marker-GFP RNA is injected into one-cell stage embryos. For nulcei, H2B-RFP is commonly used as marker, whereas memb-mCherry, Ecad-RFP, Ecad-GFP, or Ezrin-RFP can be used for membrane monitoring (Figure 1) [32,34,65]. Figure 1C shows an example of using the nuclear marker H2B-GFP and the membrane marker Ecad-GFP.…”

“…A combination of confocal and two-photon excitation (2PE) luorescence microscopy can be used to follow and characterize diferent morphogenetic changes in developing embryos such as cell division, polarity, ilopodia formation and dynamics, compaction, and blastocyst cavitation (Figure 1). For this aim, speciic luorescently tagged proteins or peptides are used to label nuclear, cytoplasmic, or membrane constituents and optimized confocal and 2PE luorescence imaging methods [29,31,65]. These imaging conditions allow the scan of a single embryo at intervals down to less than 60 s and reconstruction of 3D embryo morphology using Imaris (Bitplane AG) or ZEN (Zeiss) software.…”

Moving Inward: Establishing the Mammalian Inner Cell Mass

“…In this issue of Developmental Cell , Samarage et al (2015) shed light on how these cells move inward. …”